The objective of this project is to isolate, characterize and determine the mechanisms of action of certain factors, present in serum, that are required for growth and cell division of mammalian cells. Normal and malignant cells differ greatly in their requirements for certain of these serum factors, with malignant cells requiring much less of the factors. The molecular basis for the differing requirements will be investgated in order to understand the fundamental differences between the control of growth of normal and malignant cells. Emphasis will be placed on the further purification of several of the serum factors that have been identified thus far: (1) the serum factor that limits 3T3 cell density, (2) the serum factor that promotes migration of 3T3 cells on the substatum, (3) the several factors that lead to initiation of DNA synthesis in quiescent 3T3 cells, and (4) the serum factor that promotes the uptake of phosphate ion by 3T3 cells. Eventually it is hoped that individual pure serum factors will be available for use in place of serum to manipulate mammalian cell growth.